Enteric coating solutions have been provided in the past, but have required the use of organic solvents. The organic solvents tend to pollute the atmosphere and present problems of safety and hygiene for workers, so it is necessary to take steps to prevent such pollution and this involves the use of expensive equipment. Also, organic solvents present a danger of fire or explosion, and expensive equipment is required to limit or reduce this danger.
Aqueous enteric coatings insoluble in gastric juices and soluble in the intestines have previously been proposed, but they have had problems including not providing sufficient protection against moisture penetration to the interior of the tablet. Also, tablets coated with such aqueous enteric coatings tend to disintegrate in the gastric juices of the stomach and to release their medicament prematurely into the stomach, rather than delaying tablet disintegration and release of ingredients until the tablet reaches the intestines as desired.
In Shinetsu U.S. Pat. No. 4,017,647, hydroxypropyl methyl cellulose phthalate, HPMCP, is dissolved in water and neutralized with a base and is applied to tablets by spray coating, but the coatings are not enteric until they undergo a subsequent acid treatment step.
J. W. Stafford, Sandoz AG, in Drug Development and Industrial Pharmacy, 8(4), 513-530 (1982), discloses a completely aqueous enteric film coating spray system with neutralized HPMCP for the enteric coating of tablets whereby 12.5% by wt. of HPMCP is dispersed in water and neutralized with base to make a spray solution, with the amount of base required per 100 g. HPMCP being 11.8 g. of 25% aqueous ammonia, 6.74 g. of NaOH (added dissolved in a little water for rapid dispersion), or 25.3 g. triethanolamine. The HPMCP is said to be usually dissolved after a few hours. Insoluble excipients such as talc and titanium dioxide are ball milled as aqueous dispersions before being added to the spray solution. The neutralized HPMCP film former is completely water soluble. To provide enteric protection, the neutralized HPMCP film on the tablet is converted to insoluble acid at the gastric juice pH, which is generally said to be about 1 to 3 pH.
Shinetsu Japanese Pat. No. 104,823/1981 discloses intestinally soluble protective coating agent composites for solid medicines characterized by dispersing a powdery intestinally soluble coating base agent having an average particle size of smaller than 100 microns in an aqueous medium containing a plasticizer sparingly soluble in water. It is advisable to add an appropriate dispersion aid or emulsifier to promote the dispersion or emulsion of the plasticizer. To prevent agglomeration of the coating dispersion, it is desirable to keep the temperature below 30.degree. C. in the spray guns and pipes so as to avoid clogging of the pipes or spray gun nozzles.
Accordingly, it has been a problem to prevent the heat from jelling or coalescing the coating solution or dispersion in the spray equipment and causing the equipment to clog.
Japanese Pat. No. 104,823/1981 to Sekikawa et al. relates to intestinally soluble protective coating agent composites for solid medicines and teaches that the use of water soluble plasticizers destroys the enteric performance because such plasticizers are not resistant to gastric juices and do not prevent the tablet from disintegrating in the stomach.
Also, the Japanese patent discloses preparing a coating system by adding individual components: adding a wetting agent to water, dispersing a polymer into the water, adding a plasticizer, etc. The inventive system contemplates adding only one ingredient to water to make the coating dispersion, and that ingredient is the coating dry powder. However, the inventive dry powder system had to overcome problems of premature agglomeration and clogging in the spray apparatus. This problem was overcome by adding an ammonia solution after mixing and thoroughly wetting the coating dry powder particles in water.